New studies suggest that analysis of circulating tumor cells (CTCs) is valuable for prognostic risk stratification and probably treatment monitoring and early diagnosis—perhaps even the future development of drugs that can disrupt metastasis. Although it is not yet clear that switching chemotherapies based on CTC measurements improves patient survival, microfluidic cell capture technologies are proliferating and the long-sought goal of “liquid biopsies” of tumors may soon be at hand. Using these technologies, it might be possible to personalize therapy regimens by testing CTCs in the lab, without subjecting patients to unnecessary toxicities.
In the decade since the CellSearch® platform was first validated in a small prospective study in 2004, several small, mostly retrospective studies have lent support to the hypothesis that measurements of epithelial tumor cell concentrations (or circulating tumor cells [CTCs]) in the peripheral blood stream can predict treatment outcomes among patients with carcinomas of the breast, prostate, ovaries, colon, and lung, and possibly even those with neuroendocrine tumors.1-8
It has long been assumed that CTCs emerge in advanced cancers prior to and during metastasis, but one recent study in patients with pancreatic cystic lesions suggests that CTCs might one day allow for screening and early detection of tumorigenesis before detectable tumors have formed.9
CTC analysis has not yet been widely adopted in standard clinical guidelines or recommendations for patient risk assessment or treatment monitoring; however, that is because no large, definitive prospective studies have been available.10
But now, the largest assessment to date of CTC enumeration in patients with metastatic breast cancer treated with standard therapies has confirmed that CTCs are strongly and independently predictive of progression-free survival (PFS) and overall survival (OS).11 The authors of this study concluded that CTC counts just 1 month after treatment initiation distinguishes patients with treatment-sensitive cancer from those with aggressive, treatment-resistant disease.11 The pooled analysis of data for 1,944 patients treated at 17 European cancer centers confirmed the findings of the 2004 study: 5 or more CTCs per 7.5 mL were identified among the 911 patients with the most aggressive cancers, whose PFS and OS times were compared with those of patients with lower CTC counts at baseline (hazard ratios [HRs], 1.92 [95% CI, 1.73-2.14] and 2.78 [95% CI, 2.42-3.19], respectively; P<0.0001).11